Safety profiles of iron chelators in young patients with haemoglobinopathies

Botzenhardt, Sebastian; Li, Ni-Ya; Chan, Esther W.; Sing, Chor‐Wing; Wong, Ian C. K.; Neubert, Antje

doi:10.1111/ejh.12833

Cited by 33 publications

(35 citation statements)

References 169 publications

(158 reference statements)

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“…Leukopenia, being a complication of treatment, was reported in one case. 8 Deferoxamine is known to cause other complications [11][12][13] , like visual and auditory neurotoxicity due to chronic treatment, and acute effects, including abdominal pain, diarrhea, nausea, vomiting, and hypotension. None of these were reported in these cases.…”

Section: Discussionmentioning

confidence: 99%

Chelation therapy for secondary neonatal iron over load: Lessons learned from rhesus hemolytic disease

et al. 2018

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Secondary neonatal iron overload occurs with intrauterine and post-natal blood transfusions. Treatment with intravenous Deferoxamine was reported only in four cases in the literature. Herein we report a case of a patient born at 36 weeks of gestation, who had rhesus hemolytic disease. He developed secondary iron overload, causing liver injury, after a total of six blood transfusions: four intrauterine and 2 post-natal transfusion therapies. Intravenous Deferoxamine treatment was started at the age of 45 days due to a ferritin level of 40,000 mg/L, progressive rise of liver enzymes, and worsening cholestasis. Treatment resulted in marked reduction in ferritin level (down to 829 mg/L at the age of 6 months), significant improvement in the liver enzymes, and resolution of cholestasis.

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Section: Discussionmentioning

confidence: 99%

Chelation therapy for secondary neonatal iron over load: Lessons learned from rhesus hemolytic disease

et al. 2018

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“…Thus, life‐long iron chelation therapy is necessary for prevention of morbidities and for their long term survival. Iron chelation therapy is generally safe in pediatric TDT patients but deferoxamine (DFO) use in very young children with only mild iron overload has been associated with growth delay and significant bone defects due to excessive depletion of iron needed for normal biologic reactions . Delaying the start of treatment until a more severe level of iron load was reached was found to be effective in minimizing the risk of DFO‐induced toxicities.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion‐dependent thalassemia: A randomized controlled trial

Elalfy

Adly

Awad³

et al. 2017

American J Hematol

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Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N = 64 their age ranged from 10 to 18 (median 12) months, 54.7% males; receiving ≤6 transfusions; serum ferittin (SF) >400 to < 1000 ng/mL were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 μg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months postrandomization, 100% of the subjects in DC group had achieved SF > 1000 µg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level > 0.6 µM was observed in 97% vs. 40% of the DS and ES groups, respectively, (P < 0.001). The time to reach SF > 1000 µg/L was delayed by 6 months in the ES-DFP group (P < 0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group.

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“…Deferiprone is a lipid-soluble membrane-permeable iron chelator which can cross the blood-brain barrier and cellular membranes. It has been successfully used to treat iron overload in hemoglobinopathies [168]. Remarkably, it is capable of reaching mitochondrial iron deposits in all tissues including nervous system [169,170].…”

Section: Deferipronementioning

confidence: 99%

Antioxidant Therapies and Oxidative Stress in Friedreich’s Ataxia: The Right Path or Just a Diversion?

et al. 2020

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Friedreich’s ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those “antioxidant” drugs that went beyond the disease’s models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials.

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Safety profiles of iron chelators in young patients with haemoglobinopathies

Cited by 33 publications

References 169 publications

Chelation therapy for secondary neonatal iron over load: Lessons learned from rhesus hemolytic disease

Chelation therapy for secondary neonatal iron over load: Lessons learned from rhesus hemolytic disease

Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion‐dependent thalassemia: A randomized controlled trial

Antioxidant Therapies and Oxidative Stress in Friedreich’s Ataxia: The Right Path or Just a Diversion?

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